We propose to continue our multidisciplinary research program, which will integrate substantial institutional expertise in infectious diseases, neurology, immunology, retrovirology, herpes viruses and parasitology, and numerous clinical resources in both South Carolina and North Carolina, focusing on the evaluation of novel therapies for HIV-infected persons. In Part A, Adult Clinical Trials, (C. van der Horst), clinical investigators at UNC and 4 satellite units in Charlotte, Greensboro, Raleigh and Charleston, South Carolina, will study new compounds active against HIV and associated infections, malignancies and neurologic disorders in 150 new patients and follow 277 previously enrolled patients. We shall continue our high rate of accrual among minorities, women and IVDUs. Trials will be of all phases (I, II, III) and types. Patients will be followed for in vivo evidence of study drug effects on HIV, EBV, CMV, HSV and other opportunistic infections. Pharmacokinetics will be monitored in our General Clinical Research Center. Concepts for new protocols will originate by our participation in ACTG committees and by our newly established scientific advisory board. Outreach to the community will be accomplished through our community advisory boards at each site and through our statewide newsletter. Part B, Pediatric Component (W. Lim), is similar to Part A but with a focus on children and a special emphasis on adolescents infected with HIV. We shall be following 16 children and will enrol 14 more including 11 pregnant women. Part C.1, Virology Core Laboratory (S. Fiscus), will perform a minimum of 500 HIV cultures and 2600 HIV p24 antigen determinations each year in addition to continuing research in circulating immune complexes in HIV patients, the development of new markers for viral burden, and antiviral therapy of EBV.